foto

PhD M.E. Wildenberg

Positions
Associate Professor, Research Associate
Main activities
Research
Specialisation
Pathogenesis and treatment of inflammatory bowel diseases
Focus of research

My research group focusses on translational gastroenterology, in particular in inflamatory bowel disease (IBD). In close collaboration with the clinical gastroentrology and the department of surgery, several research lines have been developed combining clinical questions and basic research, all aimed at improving the efficacy of currently avaible therapeutic options and development of new interventions.

Specific research topics include:

-The effector mechanisms of current IBD medication

In IBD, nearly all commonly used medication is effective in a subset of patients, but not in all. Currently the choice of drug is often a matter of trial and error, due a lack of information regarding the efffector mechanisms of the various medications. We have focussed on the elucidation of these mechanims, in order to both improve the existing medication and predict which patient requires which treatment. This includes the evaluation of the effects of genetic polymorphisms in autophagy related genes on disease pathways and response to thiopurines, as well as the elucidation of the effector mechanim of anti-TNF. This last research has already resulted in the identification of new anti-TNF combination therapy, for which a clinicial trial will start soon.

- Involvement of extra-intestinal tissues in disease

Although the main location of IBD is the intestine, both complaints and symptoms also occur outside the gastrointestinal tract. In collaboration with the department of surgery, my group investigates the role of the mesentry in the development of disease and post-surgical healing. This results in a unique combination of basic data supporting surgical approaches, reducing complications and reinterventions.

In addition to their inestinal complaints, many IBD patients suffer from extreme fatigue, even during periods of remission. We have recently started a project studying the biology leading to this fatigue, with the ultimate aim of developing medication targeting both intestinal inflammation and fatigue.

Key publications
  • Wildenberg M. E., Koelink P. J., Diederen K., te Velde A. A., Wolfkamp S. C. S., Nuij V. J., Peppelenbosch M. P., Nobis M., Sansom O. J., Anderson K. I., van der Woude C. J., D'Haens G. R. A. M., van den Brink G. R. The ATG16L1 risk allele associated with Crohn's disease results in a Rac1-dependent defect in dendritic cell migration that is corrected by thiopurines Mucosal immunology 2017;10 (2):352-360 [PubMed]
  • Wildenberg Manon E., Vos Anne Christine W., Wolfkamp Simone C. S., Duijvestein Marjolijn, Verhaar Auke P., te Velde Anje A., van den Brink Gijs R., Hommes Daniel W. Autophagy Attenuates the Adaptive Immune Response by Destabilizing the Immunologic Synapse Gastroenterology 2012;142 (7):1493-+ [PubMed]
  • Vos Anne Christine W., Wildenberg Manon E., Duijvestein Marjolijn, Verhaar Auke P., van den Brink Gijs R., Hommes Daniel W. Anti-tumor necrosis factor-α antibodies induce regulatory macrophages in an Fc region-dependent manner Gastroenterology 2011;140 (1):221-230 [PubMed]
  • Wildenberg Manon E., Levin Alon D., Ceroni Alessandro, Guo Zhen, Koelink Pim J., Hakvoort Theodorus B. M., Westera Liset, Bloemendaal Felicia M., Brandse Johannan F., Simmons Alison, D'Haens Geert R., Ebner Daniel, van den Brink Gijs R. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model Journal of Crohn s & colitis 2017;11 (12):1480-1490 [PubMed]
All Publications
Research programmes

PhD M.E. Wildenberg (Inflammatory Bowel Disease - Mechanisms and therapies)

My research group focusses on translational gastroenterology, in particular in inflamatory bowel disease (IBD). In close collaboration with the clinical gastroentrology and the department of surgery, several research lines have been developed combining clinical questions and basic research, all aimed at improving the efficacy of currently avaible therapeutic options and development of new interventions.

Specific research topics include:

-The effector mechanisms of current IBD medication

In IBD, nearly all commonly used medication is effective in a subset of patients, but not in all. Currently the choice of drug is often a matter of trial and error, due a lack of information regarding the efffector mechanisms of the various medications. We have focussed on the elucidation of these mechanims, in order to both improve the existing medication and predict which patient requires which treatment. This includes the evaluation of the effects of genetic polymorphisms in autophagy related genes on disease pathways and response to thiopurines, as well as the elucidation of the effector mechanim of anti-TNF. This last research has already resulted in the identification of new anti-TNF combination therapy, for which a clinicial trial will start soon.

- Involvement of extra-intestinal tissues in disease

Although the main location of IBD is the intestine, both complaints and symptoms also occur outside the gastrointestinal tract. In collaboration with the department of surgery, my group investigates the role of the mesentry in the development of disease and post-surgical healing. This results in a unique combination of basic data supporting surgical approaches, reducing complications and reinterventions.

In addition to their inestinal complaints, many IBD patients suffer from extreme fatigue, even during periods of remission. We have recently started a project studying the biology leading to this fatigue, with the ultimate aim of developing medication targeting both intestinal inflammation and fatigue.

Postdocs
PhD P.J. Koelink

Others
BSc M. van Roest

Prof. MD PhD G.R. van den Brink (Intestinal mucosal homeostasis and it's deregulation in inflammatory bowel disease and during oncogenesis)

Current research funding
  • AMC
  • Boehringer Ingelheim
  • GSK Service Unlimited (CERPS UK, JDE & UK GMS)
  • Life Sciences Health TKI
  • Nutricia Research B.V.
  • Robarts Clinical Trials B.V,
  • Stichting AMC Foundation
  • ZonMw